Phase I Interaction Study of Istaroxime and Digoxin in Subjects With Stable Heart Failure

NCT00869115 | Withdrawn Phase 1 DMC

• 2 other identifiers: Debio 0614-106PAREXEL Study Number : 98378
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study explores a potential drug-drug interaction between istaroxime and digoxin in patients with stable CHF on chronic oral digoxin treatment.

Conditions

Heart Failure

Keywords

Digoxin; Inotropes; Lusitropic agents; Istaroxime; Debio 0614

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic endpoints : Istaroxime PK parameters: - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) plasma concentrations - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) urine concentrations

• Pharmacokinetic endpoints : Digoxin PK parameters: - Digoxin plasma concentrations

• Safety endpoints: - Incidence of adverse events; - Change in vital signs; - Change in 12-lead ECG parameters; - Incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous EC

• Pharmacodynamic endpoints: - Change in echocardiographic parameters; - Change in SBP; - Change in non invasive cardiac output (Impedance cardiography) parameters.

Study Arms (4)

1

EXPERIMENTAL

TREATMENT 0.5 μg/kg/min

Drug: Istaroxime

2

EXPERIMENTAL

TREATMENT 1.0 μg/kg/min

Drug: Istaroxime

3

EXPERIMENTAL

TREATMENT 1.5 μg/kg/min

Drug: Istaroxime

4

PLACEBO COMPARATOR

PLACEBO

Drug: Istaroxime

Interventions

Istaroxime DRUG

Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent;
• Male or female patients ≥18 years;
• Female patients of childbearing potential must not be pregnant;
• Chronic stable cardiac function impairment (no change in heart failure medication over the last 3 months and without any dosage adjustment in the last 4 weeks);
• Systolic blood pressure (SBP) of ≥ 90 mmHg and ≤ 140 mmHg;
• LVEF ≤ 35% by any method (to be performed at screening if not measured within the last 12 months);
• Chronic treatment (i.e. once daily dosing without interruption) with oral digoxin started at least 3 months prior to study entry and without any concomitant administration of other positive inotropic drugs;

You may not qualify if:

• Need for current or intermittent intravenous positive inotrope administration within the preceding 6 months, or hemodynamic support devices;
• Acute coronary syndrome within the past 3 months;
• Coronary artery bypass graft or percutaneous coronary intervention within the past 3 months;
• Stroke within the past 6 months;
• Atrial fibrillation or uncontrolled heart rate (HR) (\> 100 beats per minute \[bpm\]);
• Significant arrhythmia or second or third degree atrio-ventricular block;
• Valvular disease as the primary cause of HF;
• Significant ECG abnormalities as assessed by appropriately qualified physician or investigator including QTcF \>450;
• Positive testing for Human Immunodeficiency Virus (HIV), Hepatitis B and/or Hepatitis C;
• HR \> 100 bpm or \< 50 bpm;
• Serum potassium \> 5.3 mmol/L or \< 3.8 mmol/L and magnesium \> 1.1 mmol/L or \< 0.6 mmol/L,
• TN I \> ULN.

Sponsors & Collaborators

• Debiopharm International SA: lead

Related Publications (1)

• Gheorghiade M, Blair JE, Filippatos GS, Macarie C, Ruzyllo W, Korewicki J, Bubenek-Turconi SI, Ceracchi M, Bianchetti M, Carminati P, Kremastinos D, Valentini G, Sabbah HN; HORIZON-HF Investigators. Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure. J Am Coll Cardiol. 2008 Jun 10;51(23):2276-85. doi: 10.1016/j.jacc.2008.03.015. Epub 2008 Apr 9.

  PMID: 18534276 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

Istaroxime

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 24, 2009
• First Posted: March 25, 2009
• Study Start: June 1, 2009
• Last Updated: October 23, 2014

Record last verified: 2014-10